[HTML][HTML] Synthetic and immunological studies on the OCT4 immunodominant motif antigen-based anti-cancer vaccine

T Chen, K Liu, J Xu, T Zhan, M Liu, L Li… - Cancer Biology & …, 2020 - ncbi.nlm.nih.gov
T Chen, K Liu, J Xu, T Zhan, M Liu, L Li, Z Yang, S Yuan, W Zou, G Lin, DA Carson, CCN Wu…
Cancer Biology & Medicine, 2020ncbi.nlm.nih.gov
Objective: Cancer stem cell is one of the important causes of tumorigenesis as well as a
drug target in the treatment of malignant tumor. However, at present, there is no immune
vaccine targeting these cells. Octamer-binding transcription factor 4 (OCT4), a marker of
embryonic stem cells and germ cells, often highly expresses in the early stages of
tumorigenesis and is therefore a good candidate for cancer vaccine development. Methods:
To identify the optimal carrier and adjuvant combination, we chemically synthesized and …
Abstract
Objective: Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor. However, at present, there is no immune vaccine targeting these cells. Octamer-binding transcription factor 4 (OCT4), a marker of embryonic stem cells and germ cells, often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine development.
Methods: To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein, keyhole limpet hemocyanin (KLH), combined with Toll-like receptor 9 agonist (TLR9).
Results: Immunization with OCT4-3+ TLR9 produced the strongest immune response in mice. In prevention assays, significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3+ TLR9 (P< 0.01). Importantly, the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with TLR9. Meanwhile, multiple cytokines [such as interferon (IFN)-γ (P< 0.05), interleukin (IL)-12 (P< 0.05), IL-2 (P< 0.01), and IL-6 (P< 0.05)] promoting cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3+ TLR9. Moreover, we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation vaccines.
Conclusions: Collectively, these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response, leading to the suppression of primary tumor growth in testis embryonic carcinoma.
ncbi.nlm.nih.gov
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